Summary: Sigma-1 receptors subdue systemic inflammation, which can be lethal, as in the case of septic shock. Mice lacking the endoplasmic reticulum sigma-1 receptor had exacerbated responses to LPS (lipopolysaccharides) or fecal slurry. The antidepressant fluvoxamine can bind sigma-1 and acts as a receptor agonist. Therapeutic treatment of mice in two inflammatory models revealed that fluvoxamine lowered inflammatory cytokine production and improved survival. The authors suggest that repurposing fluvoxamine to enhance sigma-1 receptor activity may be beneficial for treating sepsis.
Rosen DA, Seki SM, Fernández-Castañeda A, Beiter RM, Eccles JD, Woodfolk JA, Gaultier A: Modulation of the signa-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis. Sci Transl Med. 11, (478), Feb. 6, 2019; eaau5266; DOI: 10.1126/scitranslmed.aau5266.